Scientists identify 'hub' of fear memory in brain cells

London, September 29 : Experiments on mice conducted by Emory University researchers have revealed that a protein required for the earliest steps in embryonic development, beta-catenin, also plays a key role in solidifying fear memories in the brain.

Study leader Dr. Kerry Ressler, associate professor of psychiatry and behavioural sciences at Emory University School of Medicine, says that beta-catenin can be a potential target for drugs to enhance or interfere with memory formation.

For probing beta-catenin's role in fear memory formation, Ressler and his graduate student Kimberly Maguschak used a variety of approaches to probe beta-catenin's role in fear memory formation - such as stabilizing the protein with a pulse of the psychiatric drug lithium, and injecting a virus that could remove the gene for beta-catenin from brain cells.

The researchers made the mice learn to dread a certain tone that was followed by an electrical shock, and the animals would show that fear by freezing.

"We found that after beta-catenin is taken out, the mice can still learn to fear the shocks. But two days later, their fear doesn't seem to be retained because they spend half as much time freezing in response to the tone," Nature magazine quoted Maguschak as saying.

She said that beta-catenin appeared to be turned on in the amygdala - a brain region thought to be important for forming memories of emotionally charged events - and involved in signalling during the learning process.

"However, after the process of moving memories from short-term to long-term is complete, beta-catenin doesn't appear to be necessary anymore," she said.

"Injecting the virus after that point has no effect on the ability of the mice to express their fear memory," she added.

The researchers also observed that lithium salts, when given to the mice before training, made them even more afraid of the tone two days later.

Chemically, lithium inhibits an enzyme that usually targets beta-catenin for destruction, causing beta-catenin to become more active.

Maguschak, however, insisted that lithium was an imprecise tool for studying beta-catenin because it affects several enzymes in the brain.

Ressler added: "Psychiatrists have used lithium to treat mania and bipolar disorder for decades, but how it works is not well-understood. Importantly, we gave the mice one acute dose of lithium, rather than letting it build to a stable level like in the clinical situation. It's not clear whether there is a connection between mood regulation and how lithium functions in our experiments with fear memory."

Based on their observations, the researchers came to the conclusion that medications that inhibit beta-catenin could transiently interfere with memory formation after trauma, helping to prevent post-traumatic stress disorder.

They further said that medications that enhance beta-catenin function within the brain might serve as new therapies to treating disorders of memory, such as Alzheimer's disease.

Ressler revealed that his team was planning to dissect the contribution of beta-catenin's different functions: cell adhesion and developmental signaling.

According to him, when over-activated by genetic mutations, beta-catenin could drive tumour formation in several tissues, such as the colon, the skin and the kidney.

"It's possible we will see that a number of genes involved in cancer also are involved in learning and memory," he says.

A research article describing the study has been published in the journal Nature Neuroscience.

ANI